osteopathia striata with cranial sclerosis

Osteopathia striata with cranial sclerosis (OS-CS) is a skeletal dysplasia that primarily affects the bones, particularly seen as long, linear striations in the metaphyses of long bones along with sclerosis of the craniofacial bones. Affected individuals may present with macrocephaly, cleft palate, and hearing loss. This condition is caused by variants in the AMER1 gene and follows an X-linked dominant pattern. It is very rare, affecting fewer than 1 in 1,000,000 people, and can show a wide range of symptom severity.

The clinical presentation of OS-CS is marked by distinctive bone abnormalities such as longitudinal striations in the long bones, coarse metaphyseal trabecularization, osteopetrosis, and increased bone mineral density. Patients often exhibit notable craniofacial features including facial hyperostosis, macrocephaly, a prominent forehead, and cleft or high, narrow palates. Additionally, a number of affected individuals experience neurodevelopmental challenges, with some presenting with mild intellectual disability, global developmental delay, or echolalia. Not all individuals experience all of these features, and severity varies considerably.

This condition arises from pathogenic variants in the AMER1 gene. It is inherited in an X-linked dominant manner, meaning that the altered gene on the X chromosome can cause the condition in individuals who inherit it, with females typically being affected and potentially exhibiting a range of symptom severity due to skewed X-inactivation. While some cases may result from de novo variants, genetic counseling is recommended to understand the implications for the family and discuss reproductive options.

Currently, there are no FDA-approved treatments specifically targeting osteopathia striata with cranial sclerosis. Management focuses on supportive care and symptom management, with treatment plans tailored to an individual’s clinical presentation. A multidisciplinary approach is recommended, involving specialists such as orthopedists, audiologists, and speech therapists, along with regular surveillance to monitor for potential complications. Patients should discuss treatment options with their healthcare team and consider genetic counseling for a comprehensive evaluation of care and family planning.

Outcomes in osteopathia striata with cranial sclerosis vary widely between individuals, reflecting the broad spectrum of bone and neurodevelopmental involvement. With current standards of care and ongoing advancements in supportive therapies, many individuals experience a stable or slowly evolving course. It is important to recognize that severity and specific symptoms differ significantly from person to person, and modern management strategies continue to improve quality of life. Families often find it helpful to connect with specialists familiar with this condition, and genetic counseling can provide valuable guidance for long-term management and family planning.